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This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 294/5/G1171    most recent 00360.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by de Vogel-van den Bosch, H. M. Articles by van der Meer, R. Search for Related Content PubMed PubMed Citation Articles by de Vogel-van den Bosch, H. M. Articles by van der Meer, R.

MUCOSAL BIOLOGY

A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine

¹Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen; ²Nutrigenomics Consortium, TI Food and Nutrition, Wageningen; ³Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University-Medical Center Groningen, Groningen; ⁴Department of Pediatrics/Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam; and ⁵NIZO Food Research, Ede, The Netherlands

Submitted 9 August 2007 ; accepted in final form 12 March 2008

Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-binding cassette transporters Abca1 and Abcg5/Abcg8 are presumed to be involved in cholesterol efflux from the enterocyte toward plasma HDL and back into the intestinal lumen, respectively. Abca1, Abcg5, and Abcg8 are well-established liver X receptor (LXR) target genes. We examined the effects of a high-fat diet on expression and function of cholesterol transporters in the small intestine in mice. Npc1l1, Abca1, Abcg5, and Abcg8 were all downregulated after 2, 4, and 8 wk on a cholesterol-free, high-fat diet. The high-fat diet did not affect biliary cholesterol secretion but diminished fractional cholesterol absorption from 61 to 42% (P < 0.05). In an acute experiment in which triacylglycerols of unsaturated fatty acids were given by gavage, we found that this downregulation occurs within a 6-h time frame. Studies in LXR-null mice, confirmed by in vitro data, showed that fatty acid-induced downregulation of cholesterol transporters is LXR independent and associated with a posttranslational increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity that reflects induction of cholesterol biosynthesis as well as with a doubling of neutral fecal sterol loss. This study highlights the induction of adaptive changes in small intestinal cholesterol metabolism during exposure to dietary fat.

cholesterol absorption; ABC transporters; Npc1l1; fatty acids